Atom-ProteinQA: Atom-level protein model quality assessment through fine-grained joint learning.

MOTIVATION: Protein model quality assessment (ProteinQA) is a fundamental task that is essential for biologically relevant applications, i.e., protein structure refinement, protein design, etc. Previous works aimed to conduct ProteinQA only on the global structure or per-residue level, ignoring potentially usable and precise cues from a fine-grained per-atom perspective. In this study, we propose an atom-level ProteinQA model, named Atom-ProteinQA, in which two innovative modules are designed to extract geometric and topological atom-level relationships respectively. Specifically, on the one hand, a geometric perception module exploits 3D sparse convolution to capture the geometric features of the input protein, generating fine-grained atom-level predictions. On the other hand, natural chemical bonds are utilized to construct an atom-level graph, then message passing from a topological perception module is applied to output residue-level predictions in parallel. Eventually, through a cross-model aggregation module, features from different modules mutually interact, enhancing performance on both the atom and residue levels. RESULTS: Extensive experiments show that our proposed Atom-ProteinQA outperforms previous methods by a large margin, regardless of residue-level or atom-level assessment. Concretely, we achieved state-of-the-art performance on CATH-2084, Decoy-8000, public benchmarks CASP13 & CASP14, and the CAMEO. AVAILABILITY: The repository of this project is released on: https://github.com/luyfcandy/Atom_ProteinQA.

CAJAL enables analysis and integration of single-cell morphological data using metric geometry.

High-resolution imaging has revolutionized the study of single cells in their spatial context. However, summarizing the great diversity of complex cell shapes found in tissues and inferring associations with other single-cell data remains a challenge. Here, we present CAJAL, a general computational framework for the analysis and integration of single-cell morphological data. By building upon metric geometry, CAJAL infers cell morphology latent spaces where distances between points indicate the amount of physical deformation required to change the morphology of one cell into that of another. We show that cell morphology spaces facilitate the integration of single-cell morphological data across technologies and the inference of relations with other data, such as single-cell transcriptomic data. We demonstrate the utility of CAJAL with several morphological datasets of neurons and glia and identify genes associated with neuronal plasticity in C. elegans. Our approach provides an effective strategy for integrating cell morphology data into single-cell omics analyses.